Based, in part, on some striking similarities between histidine decarboxylase in the rat gastric mucosa and ornithine decarboxylase in the duodenum it is postulated that the induction of histidine decarboxylase is associated with the trophic actions rather than the acid secretory properties of gastrin. This proposal seeks to investigate several ramifications of this hypothesis. First, the cell types(s) in the rat gastric mucosa containing inducible histidine decarboxylase will be identified. Histidine decarboxylase will be purified to homogeneity by ion exchange chromatography, isoelectric focusing, affinity chromatography and gel filtration. Antibody to the enzyme, raised in rabbits, will be partially purified by salt fractionation and ion exchange chromatography. The histidine decarboxylase containing cell will be identified using the protein A-colloidal gold immunocytochemical procedure and electron microscopy. The distribution of the histidine decarboxylase cell will be compared to that of the ECL and A cells known to contain histamine to establish if all the histamine in the mucosa is closely associated with the enzyme. Second, methods will be developed for the preparation and separation of histidine decarboxylase cells. Cell suspensions will be prepared by pronase/collagenase digestion and separated by density sedimentation at unit gravity. The cell fractions will be analyzed by electron microscopy and biochemical composition to determine if ECL, A and/or histidine decarboxylase cells can be separated by this technique. Further purification of histidine decarboxylase cells will be attempted using an affinity matrix coupled to gastrin. Third, the possibility that histidine decarboxylase cells possess histamine receptors will be investigated and the factors affecting the relationship between histidine decarboxylase and histamine will be determined in isolated cells. These studies will contribute fundamental information to our understanding of the role of histamine.